In order to account for the remarkable catalytic power of enzymes, it is generally considered that the activation free energy is contributed both by binding of the substrate to the enzyme (step 1) and by chemical manipulation of the bound substrate (bond-making and breading, step 2). Popular opinion holds that most of the activation energy is supplied in step 2: We have proposed, however, that the overall catalytic process can be explained more reasonably if it is assumed that the first step (binding) contributes a more significant, and sometimes major, share of the activation energy. To support this theory, we have synthesized a large variety of test-tube models which simulate the bound substrate by being frozen into a single, favorable conformation and by having the interacting groups brought into the closest possible juxtapositio (sterepopulation control). These compounds undergo intramolecular reactions at rates compare to those catalyzed by enzymes. Sometimes even too fast to measure. The protein raises both the entropic and enthalpic components of the substrate by binding it in a single, rigid conformation. Recent work has involved the synthesis of compounds designed (1) to evaluate the flexibility of conformationally forzen carbon chains by ring-ring interconversion and (2) to study steric and electronic effects of 1H and 13C nmr spectra through space rather than through covalent bonds. As part of our studies of practical applicatoin of stereopopulaiton control, we are currently exploring the use of o-nitroaryl derivatives of biogenic amines and antibiotics as prodrugs. The intent is to facilitate passage from got to circulatory system and from circulatory system to brain by temporary masking of charge within the molecule.